A313G Glutathione S-transferase P1 polymorphism: Frequency in Croatian population and risk of Alzheimer's disease

Background and Purpose: Alzheimer's disease (AD) is a neurodegenerative disorder of unknown etiology. Many chemicals can affect the nervous system and some of them require metabolic activation to induce their toxic effects, so genetic polymorphism that encodes defective forms of detoxifying enzymes can further increase the risk of exposure to neurotoxicants. Glutathione transferases (GSTs) are a multiple gene family of phase 11 enzymes that catalyse conjugation of glutathione to numerous potentially toxic compounds and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. The pi class of GST (GSTPI) is the most ubiquitous and prevalent GST i.soenzyme in non-hepatic tissues. The aim of this study was to determine thegenotype distribution for the A313G GSTPI exon 5 polymorphism in healthy subjects, and to investigate the association between GSTPI polymorphism and Alzheimer's disease. Materials and Methods: The A313G GSTPI genotypes were determined by PCR-RFLP method in 180 healthy controls and 40 patients with Alzheimer's disease. Results: Analysisshowed homozygous mutant (GG) genotype in 20% of AD patients and 8% of controls, heterozygous (AG) genotype in 25% ofpatients and 46% of controls, while wild type (AA) genotype was detected in SS% of patients and 46% of controls. There was a stata'.stically significant dzfference between AD patients and controls in the distribution frequency ofA3l3G GSTPI genotypes (p=0.012) due to higher prevalence of mutant GG genotype in AD. Additionally, statistically significant increase in Alzheimer s disease risk (OD=2.964, CI=1.149-7.646) wasfound to correlate with homozygous mutant (GG) genotype. Conclusions: Our results demonstrate that the A313G GSTPI exon 5 polymorphism could be associated with Alzheimer's disease risk.